CYP1A1 and CYP1B1 polymorphisms as modifying factors in patients with pneumoconiosis and occupationally related tumours: A pilot study

Our plain-English summary of CYP1A1 and CYP1B1 polymorphisms as modifying factors in patients with pneumoconiosis and occupationally related tumours: A pilot study, by J. Schneider, U. Bernges (Molecular Medicine Reports, 2009).

The study

• Authors: J. Schneider, U. Bernges
• Journal: Molecular Medicine Reports
• Published: 2009;2(6):1023-8
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

CYP1A1 and CYP1B1 are involved in the metabolism of carcinogens. The effect of CYP1A1 and CYP1B1 polymorphisms as genetic modifiers of risk was investigated in individuals with asbestos, silica dust or ionizing radiation-induced occupational tumours compared to exposed non-cancer subjects suffering from pneumoconiosis, particularly in relation to tobacco smoking. CYP1A1 T6235C, CYP1A1 A4889G and CYP1B1 codon 432 polymorphisms were determined by real-time PCR analysis in patients with asbestos-related lung cancer (n=39), patients with diffuse malignant mesotheliomas (n=19), lung cancer in silicosis patients (n=7), uranium miners with lung cancer (UMLC) (n=40), patients with asbestosis (n=181), and silicosis patients (n=204). The results were compared to those from a healthy unexposed control group (n=50) not exposed to carcinogenic (or fibrogenic) agents in the workplace. An additional healthy control group (n=134) comprised smokers and ex-smokers. Allele frequencies were within the range described for Caucasians. Multivariate analysis revealed that patients with occupational diseases with the susceptible CYP1A1 T6235C genotype had a calculated risk ranging from OR=0.5 (95% CI 0.18-1.36) for UMLC to OR=1.23 (95% CI 0.39-4.05) for uranium miners with silicosis. The risk for patients with the susceptible CYP1A1 A4889G allele was calculated as being between OR=0.39 (95% CI 0.10-1.54) for mesothelioma patients and OR=1.54 (95% CI 0.49-4.89) for UMLC. CYP1B1 Val432Leu polymorphisms were associated with a risk of OR=0.56 (95% CI 0.2-1.55) for UMLC and OR=1.52 (95% CI 0.68-3.39) for asbestos-exposed lung cancer patients. By analyzing the interaction between tobacco smoking, type of exposure to carcinogens and the genotypes, it was determined that smoking and the presence of the susceptible genotypes did not have a combined effect. In this pilot study, the analyzed polymorphism had no consistent modifying effect on pneumoconiosis or occupationally related tumours.

In plain English

This pilot study from Germany asked whether common inherited variants in two genes, CYP1A1 and CYP1B1, which help process cancer-causing chemicals, changed the risk of work-related lung disease and cancer. The authors tested blood DNA from people with asbestos-related lung cancer (39), diffuse malignant mesothelioma caused by asbestos dust (19), lung cancer in silicosis patients (7), former uranium miners with lung cancer linked to radiation (40), asbestosis (181), silicosis (144) and silicosis in uranium miners (60). They compared these groups with 184 people without workplace exposure to these agents, adjusting for age, sex and smoking. The authors reported no significant differences in gene variant patterns between controls and tumour patients. In mesothelioma patients the odds ratios for the three variants were 1.12 (95% CI 0.30-4.14), 0.39 (0.10-1.54) and 0.63 (0.20-2.03). The authors concluded that the variants were not associated with tumour risk and did not significantly modify risk in relation to smoking, whether the exposure was to asbestos, silica dust or ionizing radiation. They noted that some patient groups were small, so significant results could not be expected.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Pilot case-control genetic study comparing gene variant (polymorphism) frequencies in patients with occupational diseases against unexposed controls, using logistic regression
• Who was studied: Germany (uranium miners from SDAG Wismut; patients obtained through clinics for occupational diseases in Bad Reichenhall and Falkenstein). Groups: asbestos-related lung cancer (n=39), diffuse malignant mesothelioma caused by asbestos dust (n=19), lung cancer in silicosis patients (n=7), former uranium miners with lung cancer (n=40), asbestosis (n=181), silicosis (n=144), uranium miners with silicosis (n=60). Controls: 184 people without occupational exposure (50 never-smokers and 134 smokers or ex-smokers). The study period is not stated.
• Exposure: Occupational asbestos dust (fiber type not specified), silica dust, and ionizing radiation (radon and its decay products) in uranium miners, plus tobacco smoking in pack-years. Asbestos-related lung cancer was defined by asbestosis, pleural plaques or cumulative asbestos exposure of 25 fibres/ml x years. The genes studied were CYP1A1 T6235C, CYP1A1 A4889G and CYP1B1 codon 432 (Val432Leu).
• Main results:
  • No significant differences in CYP1A1 or CYP1B1 genotype distribution between control subjects and tumour patients, and no differences by type of exposure among the occupational diseases
  • CYP1A1 T6235C: OR=0.50 (95% CI 0.18-1.36) for lung cancer due to ionizing radiation and OR=1.26 (95% CI 0.39-4.05) for uranium miners with silicosis (adjusted for age, gender and pack-years)
  • Mesothelioma due to asbestos, according to Table I: CYP1A1 T6235C OR 1.12 (0.30-4.14); CYP1A1 A4889G (labelled Ile462Val in the table) OR 0.39 (0.10-1.54); CYP1B1 Val432Leu OR 0.63 (0.20-2.03)
  • Asbestos-induced lung cancer, according to Table I: CYP1A1 T6235C OR 0.70 (0.27-1.81); CYP1A1 A4889G OR 0.51 (0.14-1.83); CYP1B1 Val432Leu OR 1.52 (0.68-3.39)
  • Gene-asbestos, gene-silica and gene-radiation interactions were inconsistent. Patients with asbestosis or asbestos-exposed lung cancer had lower risk with the CYP1A1 variants, while patients with mesothelioma due to asbestos who had the CYP1A1 T6235C variant had an elevated risk.
  • In the smoking analysis, only smokers with the wild-type CYP1A1 A4889G genotype showed a significantly elevated risk (OR=4.94; 95% CI 1.53-15.95). The highest risk among smokers with wild-type CYP1A1 was in mesothelioma patients (OR=2.23; 95% CI 0.25-19.87; CYP1A1 T6235C).
  • Smoking and the CYP1B1 variant did not have a combined effect on occupational disease
• The authors' conclusion: The authors concluded that the CYP1A1 variants were not associated with tumour risk in occupationally induced tumours and did not significantly modify risk in relation to cigarette consumption. They found no association between CYP1B1 variants, smoking and occupational diseases, whether the exposure was to asbestos, silica dust or ionizing radiation. They also wrote that the lack of association with mesothelioma supports the notion that polycyclic aromatic hydrocarbons may not have a direct effect on that cancer.
• Limitations the authors state:
  • Some patient groups were small, so significant results could not be expected
  • Examining all possible interactions greatly inflates the number of hypotheses tested
  • Less frequent variants would require a very large study (more than 10,000), which cannot be reached given the number of occupational tumour cases, especially mesothelioma, compensated each year in Germany

Topics

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Lung Cancer, Malignant Mesothelioma, Silicosis, Carcinogenic, Fibrogenic, Multivariate Analysis, Occupational Disease.

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